scholarly journals Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
W. Barcellini ◽  
B. Fattizzo
Keyword(s):  
Differential Diagnosis ◽  
Lactate Dehydrogenase ◽  
Hemolytic Anemia ◽  
Clinical Severity ◽  
Laboratory Evaluation ◽  
Intravascular Hemolysis ◽  
Compensatory Response ◽  
Autoimmune Reaction ◽  
Poor Prognostic Factor ◽  
Chronic Hemolysis

Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20–40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans’ syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions.

Hydroxycarbamide Is Related with Higher Expression of Band-3 and CD59 in Sickle Erythrocytes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4913-4913
Author(s):  
Grazielle Mecabo ◽  
Mihoko Yamamoto ◽  
Eliza Y. S. Kimura ◽  
Fabio P. Guirao ◽  
Maria Stella Figueiredo
Keyword(s):  
Lactate Dehydrogenase ◽  
Fluorescence Intensity ◽  
Protective Action ◽  
Fetal Hemoglobin ◽  
Band 3 ◽  
Median Fluorescence Intensity ◽  
Laboratory Evaluation ◽  
Corpuscular Volume ◽  
Intravascular Hemolysis ◽  
Sickle Erythrocytes

Abstract BACKGROUND: Sickle Cell Anemia (SCA) presents extra and intravascular hemolysis. The eryptosis depends on phagocytosis signs like CD47, which is known as a "don't eat me" signal. Other mechanisms associated to hemolysis, such as complement activation mediated by CD59, are poorly understood. One of the effects of hydroxycarbamide (HU) is the reduction of hemolysis, but little is known about the action of HU in these mechanisms. OBJECTIVES: To evaluate markers related to hemolysis in patients with SCA at steady state, with and without HU. METHODS: We studied 40 adult patients with SCA (n=36) or Sβ0-Thalassemia (n=4), 70% females, median age 30 years (range 18-70y). The patients were followed at the Outpatient Clinic of EPM /UNIFESP. Inclusion criteria: patients in use of HU in maximum tolerated dose for more than 1 year (G1, n=20); or without HU (G2, n=20). Exclusion criteria: pregnant women and chronic transfusion. Laboratory evaluation: CBC, reticulocyte (Ret), fetal hemoglobin (HbF), indirect bilirubin, lactate dehydrogenase (LDH), LDH isoforms, free Hb (free-Hb), haptoglobin (Hp), hemopexin, phosphatidylserine, microvesicles (Mcv), Howell-Jolly bodies (in erythrocytes and Ret), and expression of band-3, CD47 (in erythrocyte and Ret) and CD59 (in erythrocytes and Mcv). The last parameters were evaluated by flow cytometry (FACS Calibur®, BDB, San Jose, CA), using specific antibodies according to the manufacturer instructions. Data were analyzed by CellQuest® software (BDB), and the results expressed in median fluorescence intensity or percentage of positivity. Statistical analysis: Mann-Whitney test and Pearson's correlation, with significance level of 5%. RESULTS: Themean corpuscular volume and HbF were higher in G1 than G2 (p=0.033, p=0.0001, respectively) (Table 1). Free-Hb, LDH and isoforms LDH-1, -2, and -3 were lower in G1 (p=0.023, p=0.003, p=0.005, p=0.001, p=0.002, respectively). There were correlation between free-Hb and LDH-1 (r=0.45, p=0.003), LDH-2 (r=0.80, p=0.001), and LDH-3 (r=0.71, p=0.001). As expected, Hp was diminished in all patients, however G1 patients showed higher values (p=0.040). The expression of band 3 and of CD59, in erythrocytes and Mcv, were higher in G1 (p=0.001, p<0.0001 and p<0.0001, respectively). Other variables showed no statistical difference. DISCUSSION AND CONCLUSIONS: The beneficial effects of HU include decrease hemolysis, although the associated mechanisms are still unknown. Total LDH and isoforms levels were decreased in patients using HU. LDH-2 and LDH-3 showed an important correlation with free-Hb. Despite the fact that LDH-3 has been considered a nonspecific marker of tissue damage and frequently associated with lung injury, our results suggest that LDH-3 may be a valuable marker of hemolysis. The use of HU was also associated with higher levels of Hp, reinforcing its possible role on intravascular hemolysis. The higher band-3 and CD59 expression in HU patients support the protective action of this drug in sickle erythrocytes, since lower expression of these proteins have been associated with erythrocyte aging. These data present new and important insights on the effects of HU in sickle erythrocyte survival. This work was supported by FAPESP (2011/17349-0) and CAPES-SUS. Table 1: Laboratorial data. G1with HU G2without HU p Mean corpuscular volume (fL) 111.0 (86.6 - 125.0) 86.8 (71.9 - 106.6) < 0.0001 Fetal Hemoglobin (HbF, %) 12.6 (1.5 - 46.6) 6.9 (0.8 - 27.1) 0.0337 LDH (U/L) 351 (214 - 728) 526 (174 – 1,112) 0.0035 LDH -1 (U/L) 154.9 (72.1 - 361.0) 225.7 (54.1 -3,248) 0.0054 LDH -2 (U/L) 132.5 (86.5 - 361.4) 203.2 (71.9 - 421.4 ) 0.0013 LDH -3 (U/L) 33.7 (25.7 - 69.9) 56.0 (28.0 - 111.2) 0.0025 Free Hemoglobin (free-Hb, mcg/dL) 51.2 (15.1 - 248.1) 104.6 (24.9 - 286.1) 0.0239 Haptoglobin (Hp, mcg/dL) 0.6 (0 - 90.8) 0.1 (0 - 56.59) 0.0406 Microvesicles (Mcv, /µL) 21,643 (5,322 – 51,726) 32,185 (8,708 – 114,384) 0.0639 Howell Jolly in erytrocytes (x106) 5,350 (1,800 – 164,850) 2,750 (100 -75,850) 0.0829 Band-3 (MFI) 396.0 (291.6 - 461.5) 342.2 (217.7 - 388.9) 0.0010 CD47 in Ret (MFI) 164.7 (95.6 - 230.8) 146.6 (96.4 - 226.7) 0.2913 CD59 in erytrocytes (MFI) 1,039 (749.9 – 1,202) 808.0 (523.5 -1,032) <0.0001 CD59 in Mcv (MFI) 830.7 (636.4 - 1.023) 604.8 (495.9 - 802.2) <0.0001 HU = hydroxycarbamide; Ret= reticulocytes; LDH= Lactate Dehydrogenase ; MFI= median fluorescence intensity Disclosures No relevant conflicts of interest to declare.

scholarly journals Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 766-772
Author(s):  
T Coetzer ◽  
J Lawler ◽  
JT Prchal ◽  
J Palek
Keyword(s):  
Hemolytic Anemia ◽  
Genetic Defect ◽  
Clinical Severity ◽  
Lower Percentage ◽  
Structural Abnormality ◽  
Clinical Expression ◽  
Related Disorder ◽  
Asymptomatic Carriers ◽  
Hereditary Elliptocytosis ◽  
Self Association

The clinical severity of common hereditary elliptocytosis (HE) is highly variable, ranging from an asymptomatic carrier state to a severe hemolytic anemia. To elucidate the molecular basis of this variable clinical expression, we evaluated 56 subjects from 24 HE kindred, who carry alpha spectrin mutants characterized by a spectrin dimer (SpD) self-association defect related to a structural abnormality of the alpha I domain of spectrin. Twenty-nine subjects had common HE, 13 subjects have a closely related disorder, hereditary pyropoikilocytosis (HPP), and 14 are asymptomatic carriers. We compared the severity of hemolysis with the following biochemical parameters: (a) spectrin heterodimer self-association, as manifested by the percentage of SpD in the 4 degrees C low ionic strength spectrin extract; (b) spectrin structure, as examined by limited tryptic digestion of spectrin; and (c) spectrin content of the RBC membrane. Our analysis indicates that the severity of hemolysis may be correlated with quantitative differences in the percentage of SpD in the 4 degrees C spectrin extract, as well as the total spectrin content of the membrane. Thus, HPP subjects, who have the most severe hemolytic anemia, have the highest percentage of SpD as well as a decreased spectrin content. HE subjects and asymptomatic carriers, respectively, have a lower percentage of SpD and a normal spectrin content. Factors influencing these two determinants include functional differences between the individual spectrin mutants, the relative amounts of mutant spectrin present in the cells, the stability of mutant spectrin, and the possibility of a superimposed genetic defect involving spectrin synthesis.

scholarly journals Can Serum Lactate Dehydrogenase Level be Used for Predicted to IPF Clinical Severity?

2019 ◽  
Vol 20 (-1) ◽  
pp. 158-158
Author(s):  
Elif Yelda Niksarlioglu ◽  
◽  
Gungor Camsari ◽  
Mehmet Atilla Uysal ◽  
Emel Tas ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Lactate Dehydrogenase Level ◽  
Serum Lactate ◽  
Clinical Severity ◽  
Serum Lactate Dehydrogenase ◽  
Serum Lactate Dehydrogenase Level

Acne Vulgaris and Rosacea

2019 ◽  
Author(s):  
James Q Del Rosso
Keyword(s):  
Acne Vulgaris ◽  
Fibrous Tissue ◽  
Clinical Severity ◽  
European Ancestry ◽  
Laboratory Evaluation ◽  
Northern European ◽  
Chronic Disorder ◽  
Clinical Presentations ◽  
The Face

Acne vulgaris is the most common disorder seen in general dermatology practice, accounting for approximately 10% of visits each year. Both sexes and all ethnicities are affected, usually in the late preteenage or early teenage years. Both inflammatory and comedonal lesions of acne vulgaris characteristically involve the face, but truncal involvement is also relatively common. Multiple clinical presentations may be observed, with severity often progressing over time during adolescence. Severe forms of acne vulgaris can be especially disfiguring and debilitating, and are more likely to lead to permanent scarring. Therapeutic options are chosen primarily on the basis of clinical severity, with adjustments in treatment made on the basis of response or disease progression. Rosacea begins in adulthood, usually in the third decade of life or later. The disorder predominantly affects the central face in fair-skinned people, mostly those of northern European ancestry, although individuals of any race may be affected. Rosacea may present as one or more of a variety of clinical phenotypes (subtypes); it is a chronic disorder characterized by periods of exacerbation and remission. Fortunately, rosacea is not associated with scarring, although a subset of patients may develop localized proliferations of sebaceous and fibrous tissue called a phyma. Like acne vulgaris, rosacea may also adversely impact quality of life. Figures in this chapter illustrate acne vulgaris and inflammatory papules. Tables detail laboratory evaluation for women with acne vulgaris and hyperandrogenism, surgical/physical modality options for specific acne lesions and acne scars, major topical therapies for acne vulgaris, and commonly prescribed systemic therapies for acne. This chapter contains 50 references.

Acne Vulgaris and Rosacea

2012 ◽  
Author(s):  
James Q Del Rosso
Keyword(s):  
Acne Vulgaris ◽  
Fibrous Tissue ◽  
Clinical Severity ◽  
European Ancestry ◽  
Laboratory Evaluation ◽  
Northern European ◽  
Chronic Disorder ◽  
Clinical Presentations ◽  
The Face

Acne vulgaris is the most common disorder seen in general dermatology practice, accounting for approximately 10% of visits each year. Both sexes and all ethnicities are affected, usually in the late preteenage or early teenage years. Both inflammatory and comedonal lesions of acne vulgaris characteristically involve the face, but truncal involvement is also relatively common. Multiple clinical presentations may be observed, with severity often progressing over time during adolescence. Severe forms of acne vulgaris can be especially disfiguring and debilitating, and are more likely to lead to permanent scarring. Therapeutic options are chosen primarily on the basis of clinical severity, with adjustments in treatment made on the basis of response or disease progression. Rosacea begins in adulthood, usually in the third decade of life or later. The disorder predominantly affects the central face in fair-skinned people, mostly those of northern European ancestry, although individuals of any race may be affected. Rosacea may present as one or more of a variety of clinical phenotypes (subtypes); it is a chronic disorder characterized by periods of exacerbation and remission. Fortunately, rosacea is not associated with scarring, although a subset of patients may develop localized proliferations of sebaceous and fibrous tissue called a phyma. Like acne vulgaris, rosacea may also adversely impact quality of life. Figures in this chapter illustrate acne vulgaris and inflammatory papules. Tables detail laboratory evaluation for women with acne vulgaris and hyperandrogenism, surgical/physical modality options for specific acne lesions and acne scars, major topical therapies for acne vulgaris, and commonly prescribed systemic therapies for acne. This chapter contains 50 references.

Serum lactate dehydrogenase isoenzyme 4/5 ratio discriminates between hepatocarcinoma and secondary liver neoplasia

1991 ◽  
Vol 37 (8) ◽  
pp. 1419-1423 ◽  
Author(s):  
G Castaldo ◽  
G Oriani ◽  
L Cimino ◽  
M Topa ◽  
G Budillon ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Lactate Dehydrogenase ◽  
Liver Metastasis ◽  
Serum Lactate ◽  
Primary Site ◽  
The Other ◽  
Serum Lactate Dehydrogenase ◽  
Cutoff Value ◽  
Potential Index ◽  
Liver Neoplasia

Abstract Total lactate dehydrogenase (LD; EC 1.1.1.27) and its five isoenzymes were determined in sera from (a) 98 cases of cirrhosis at various stages classified according to Child and Turcotte; (b) 37 cases of hepatocarcinoma (HC) at different stages of the Okuda classification; (c) 17 patients with secondary liver neoplasia (SLN), mainly from an abdominal primary site; and (d) 19 cases of abdominal neoplasia without liver metastasis, in an attempt to contribute to the differential diagnosis between these conditions. LD-4 was enhanced in SLN and LD-5 in HC, thus indicating the LD-4/LD-5 ratio as a potential index with which to differentiate between HC and SLN patients. At a cutoff value of 1.05, 91% of these patients were correctly classified (82% for SLN and 95% for HC). Consequently, this biochemical index appears to be an efficient and rapid indicator to distinguish HC from SLN. On the other hand, the LD isoenzymes are unable to discriminate between HC and cirrhosis or between abdominal neoplasia with and without liver metastases.

Hereditary angioedema: Differential diagnosis, diagnostic tests, and family screening

2020 ◽  
Vol 41 (6) ◽  
pp. S22-S25 ◽  
Author(s):  
Michael E. Manning
Keyword(s):  
Differential Diagnosis ◽  
Hereditary Angioedema ◽  
Diagnostic Tests ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Genetic Mutation ◽  
The Body ◽  
Laboratory Evaluation ◽  
Family Screening ◽  
Common Causes

Hereditary angioedema is a rare, autosomal dominant genetic disorder that leads to sporadic episodes of swelling, which can affect any part of the body. With a prevalence of 1 in 10,000 to 1 in 50,000, there are other, more common causes of angioedema. Differentiating between bradykinin-mediated and histamine-mediated causes of swelling remains a major challenge. It is critical to develop an appropriate differential diagnosis, work through the various conditions, and obtain the pertinent laboratory evaluation to rule in or out the proposed diagnosis. As an autosomal dominant genetic disorder, there is a 50% chance with each pregnancy of passing on the genetic mutation in the SERPING1 gene. This review addressed the differential diagnosis to consider, the appropriate laboratory evaluation, and the importance of family screening.

scholarly journals Correlation between the Lactate Dehydrogenase Levels with Laboratory Variables in the Clinical Severity of Sickle Cell Anemia in Congolese Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0123568 ◽  
Author(s):  
Tite Minga Mikobi ◽  
Prosper Lukusa Tshilobo ◽  
Michel Ntetani Aloni ◽  
Georges Mvumbi Lelo ◽  
Pierre Zalagile Akilimali ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Severity ◽  
Laboratory Variables

scholarly journals Structural and functional heterogeneity of alpha spectrin mutations involving the spectrin heterodimer self-association site: relationships to hematologic expression of homozygous hereditary elliptocytosis and hereditary pyropoikilocytosis

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2235-2244 ◽  
Author(s):  
T Coetzer ◽  
J Palek ◽  
J Lawler ◽  
SC Liu ◽  
P Jarolim ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Hexagonal Structure ◽  
Clinical Severity ◽  
Related Disorder ◽  
Virtual Absence ◽  
Hereditary Elliptocytosis ◽  
Alpha Spectrin ◽  
Self Association ◽  
Partial Deficiency ◽  
Membrane Skeletons

Abstract Defects involving alpha spectrin (Sp) are found in patients with hereditary elliptocytosis and a related disorder, hereditary pyropoikilocytosis (HPP). We have previously found that the severity of hemolysis was related to the total spectrin content of the cells and the percentage of unassembled dimeric Sp (SpD) in the membranes, which, in turn, reflected the amount of mutant Sp in the cell. However, no data are available comparing differences in the function of various alpha Sp mutations to clinical severity. We now report studies of nine homozygotes or double heterozygotes for four alpha Sp mutations: alpha 1/74, alpha 1/46, alpha 1/65, and alpha 1/61, whose red blood cells (RBCs) contained only the mutant Sp and no normal Sp. Sp alpha 1/74, Sp alpha 1/46, and alpha 1/65 homozygotes differed strikingly in the severity of hemolysis that correlated with the severity of mutant Sp dysfunction, as reflected by the fraction of unassembled SpD in the membranes and the self-association of mutant Sp on inside-out vesicles. Homozygotes for Sp alpha 1/74 had a very severe hemolytic anemia and their SpD were virtually incapable of self-association, whereas SpD alpha 1/46 were not as severely affected. The Sp alpha 1/65 homozygotes had a relatively mild hemolytic anemia and their SpD showed the least impairment of function. Ultrastructural examination of membrane skeletons from subjects whose SpD self-association was severely impaired showed gross skeletal disruption and loss of hexagonal structure. In striking contrast, the homozygote for the mildly dysfunctional Sp alpha 1/65 had only a moderate disruption of the skeleton. Some of the homozygous or doubly heterozygous subjects also exhibited a partial deficiency of Sp that correlated with a RBC morphology characteristic of HPP, namely, marked microspherocytosis with virtual absence of elliptocytes. These data demonstrate striking differences in the function and structure of various alpha Sp mutants that underlie differences in clinical expression.

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